OTEZLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OTEZLA (OTEZLA).
Apremilast is a small molecule inhibitor of phosphodiesterase 4 (PDE4), which increases intracellular cyclic AMP (cAMP) levels. Elevated cAMP modulates inflammatory cytokine production, reducing TNF-α, IL-17, IL-23, and other pro-inflammatory mediators.
| Metabolism | Extensively metabolized via CYP3A4 and to a lesser extent by CYP1A2 and CYP2A6, with subsequent glucuronidation. Primary metabolite is inactive. |
| Excretion | Renal (58% as unchanged drug and metabolites; 39% as unchanged drug in urine), fecal (33% as metabolites) |
| Half-life | Terminal elimination half-life of 6-9 hours (mean 7.6 h) in healthy subjects; supports twice-daily dosing |
| Protein binding | Approximately 39% bound to plasma proteins (albumin) |
| Volume of Distribution | 0.87 L/kg (87 L for a 70 kg adult), indicating extensive extravascular distribution |
| Bioavailability | Oral: Approximately 73% (absolute bioavailability); food does not affect absorption |
| Onset of Action | Oral: Clinical improvement in psoriasis and psoriatic arthritis observed as early as 2 weeks; significant effect by 4-8 weeks |
| Duration of Action | Following discontinuation, clinical effect wanes over several weeks; psoriasis symptoms return gradually, typically within 4-8 weeks |
30 mg orally twice daily after an initial titration schedule: Days 1-2: 10 mg AM; Days 3-4: 10 mg AM, 10 mg PM; Days 5-6: 10 mg AM, 20 mg PM; Day 7 onward: 30 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: Not recommended. For severe renal impairment, use is contraindicated. |
| Liver impairment | Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Not recommended due to lack of data. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required, but consider renal function; monitor for adverse effects given potential age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OTEZLA (OTEZLA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Animal studies show excretion in rat milk. M/P ratio not determined in humans. Because of potential for serious adverse reactions, advise patients not to breastfeed during treatment and for at least 1 week after last dose. |
| Teratogenic Risk | Pregnancy Category C. No adequate and well-controlled studies in pregnant women. In animal studies, apremilast caused developmental toxicity at doses 2-3 times the MRHD (mouse) and equivalent to MRHD (monkey). First trimester: theoretical risk due to unknown effects on organogenesis; avoid unless benefit outweighs risk. Second and third trimesters: limited data; use only if clearly needed. Register patients in the Otezla Pregnancy Registry (1-877-311-8972). |
■ FDA Black Box Warning
None
| Serious Effects |
["History of hypersensitivity to apremilast or any excipients","Severe renal impairment (eGFR < 30 mL/min/1.73 m²) for psoriatic arthritis and plaque psoriasis indications as dose reduction cannot achieve adequate exposure"]
| Precautions | ["May cause severe diarrhea, nausea, and vomiting; monitor and consider dose reduction or discontinuation","May increase risk of depression; monitor mood changes and suicidal ideation especially in patients with history of depression","Weight loss reported; monitor body weight regularly","Contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) for psoriatic arthritis and plaque psoriasis; dose adjustment required for moderate renal impairment","Potential for drug interactions with strong CYP3A4 inducers (e.g., rifampin, phenytoin) which may decrease efficacy"] |
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| Fetal Monitoring | No specific fetal monitoring required. Monitor pregnant women for adverse effects similar to non-pregnant (diarrhea, nausea, headache, weight loss, depression). Ensure enrollment in pregnancy registry if exposed. |
| Fertility Effects | No impairment of fertility or reproductive function observed in male and female rats at exposures up to 2 times MRHD. Human data limited; no specific effects on fertility reported in clinical trials. |